The goal of this research program is an understanding of the changes induced in cells infected and transformed by murine C type RNA viruses. This goal will be approached first through genetic studies on in vitro virus-cell systems directed toward the isolation of viral mutants which are defective in various gene functions. Selections on the basis of host range will be used to obtain virus mutants; this method of selection is based on complementation between infecting virus and cell- associated viral gene functions. Any viral mutants obtained will be utilized as tools to study, as far as possible in biochemical terms, the individual phenotypes of the genes comprising the C type RNA viral genomes. Experiments comparing cells infected by wild type and mutant viruses will be carried out in efforts to localize the subcellular sites and determine the nature of the alterations induced by each virus. Mutant virus strains will also be injected into animals to determine possible alterations in pathology compared to that induced by the wild type strain, and to correlate such findings with those of the in vitro studies. BIBLIOGRAPHIC REFERENCES: Goldman, E. and Benjamin, T., "Analysis of Host Range of Non-Transforming Polyoma Virus Mutants," Virology 66, 372-334 (1975). Schaffhausen, B.S., and Benjamin, T.L., "Deficiency in Histone Acetylation in Non-Transforming Host Range Mutants of Polyoma Virus," Proc. Natl. Academy of Sciences, in press (1976).